Difference Between E and N Cadherin

The key difference between E and N cadherin is that E cadherin is downregulated during Epithelial-to-Mesenchymal Transition (EMT) in cancers while N cadherin is upregulated during EMT in cancers.

Cadherin is a molecule that is important in the formation of adherens junctions when binding cells with each other. Therefore, they are cell adhesion molecules which are transmembrane proteins. Cadherins depend on calcium ions in order to act. There are different types of cadherins. E cadherin and N cadherin are two types among them. They share similar structures, but they are expressed in different tissues.

1. Overview and Key Difference
2. What is E Cadherin
3. What is N Cadherin
4. Similarities Between E and N Cadherin
5. Side by Side Comparison – E vs N Cadherin in Tabular Form
6. Summary

What is E Cadherin?

E cadherin or epithelial cadherin or CDH1 is a type I classical cadherin molecule found in the epithelial tissue. The size of E cadherin molecule is 120 kDa. This molecule is greatly expressed. E cadherin forms the cadherin-catenin complex. It binds with the shorter isoform of p120 catenin. E cadherin is also referred to as suppressor of invasion since it is a potent tumour suppressor.

Figure 01: Cadherin

The loss of function of E cadherin is associated with increased invasiveness and metastasis of cancers because E cadherin is down-regulated during EMT in cancers. Therefore downregulation of E cadherin is often found in malignant epithelial cancers. Moreover, suppression of expression of E cadherin can also lead to local invasion and ultimately tumour development.

What is N Cadherin?

N cadherin is another type of cadherin that belongs to type I classical cadherins. It is known as Neuronal cadherin or cadherin-2 (CDH2). N cadherins are found in non-epithelial tissues. They are found in neural cells, endothelial cells, stromal cells, and osteoblasts. The size of N cadherin is 130 kDa. Similar to E cadherin, N cadherin is also sensitive to calcium ions. N cadherin also forms the cadherin-catenin complex. It binds with the longer isoform of catenin.

Figure 02: N Cadherin

N cadherin mainly mediates cell-cell adhesions of neuronal and some non-neuronal cell types. In blood vessels, N cadherin promotes angiogenesis by forming adhesive complexes between endothelial cells and pericyte. The upregulation of N cadherin takes place in EMT. N-cadherin induces EMT and cancer stem cell-like characteristics.

What are the Similarities Between E and N Cadherin?

E- and N-cadherin belong to type-I classical cadherins.
E and N cadherin are constituents of the adherens junction.
Both share similar molecular functions.
They are integral proteins.
They form homophilic interactions with the same molecules on other cells, thus allowing cell-cell interaction.
The upregulation of N-cadherin is followed by the downregulation of E-cadherin during EMT.
They are highly sensitive to Ca2+ and are readily degraded by proteolysis in the absence of Ca2+.

What is the Difference Between E and N Cadherin?

E cadherin is found in epithelial tissue while N cadherin is found in neural cells. So, this is the key difference between E and N cadherin. Furthermore, during EMT, E cadherin is downregulated while N cadherin is upregulated.

Moreover, another difference between E and N cadherin is that the E cadherin binds with the shorter isoform of p120 catenin while the N-cadherin binds with the longer isoform. Cadherins are important in maintaining cell and tissue structure and cellular movements. Also, they play a key role in epithelial-mesenchymal transition. EMT results in decreased cell adhesion and enhanced migration or invasion in cancers.

Below infographic lists the differences between E and N cadherin in tabular form for side by side comparison.

Summary – E vs N Cadherin

E cadherin and N cadherin are calcium dependant cell adhesion molecules. They are integral membrane proteins which form adherence junctions. E cadherin is found in epithelial tissue while N cadherin is widely expressed in neural tissue. During EMT, E-cadherin is downregulated while N cadherin is upregulated. Thus, this is the key difference between E and N cadherin.

Reference:

1. Loh, Chin-Yap, et al. “The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges.” Cells, MDPI, 20 Sept. 2019, Available here.
2. “Cadherin.” Wikipedia, Wikimedia Foundation, 30 Dec. 2020, Available here.

Image Courtesy:

1. “Adherens Junctions structural proteins” By Mariana Ruiz LadyofHats – (Public Domain) via Commons Wikimedia
2. “Localization of cadherin-catenin” By Hradabaugh – Own work (CC BY-SA 4.0) via Commons Wikimedia